Liquid chromatography (LC) is a well-known technique for separating the constituent elements in a given sample. A typical liquid LC system has a sophisticated plumbing system utilizing tubing to transfer fluid between the various components of the LC system. Various fittings are used to connect the tubing to these components. Many different types of LC systems and components for LC systems are commercially available from a number of vendors. For example, Millipore Corporation of Milford, Mass., Beckman Instruments of Fullerton, Calif., and Hewlett-Packard Company of Palo Alto, Calif., all sell LC systems, including pumps, sample injection valves, columns, and detectors, among other things.
In a typical LC system, a liquid solvent (often called the "mobile phase") is introduced from a solvent reservoir and delivered via tubing to the pump. In operation, the pump creates a vacuum which draws the solvent through the tubing and into the pump. The solvent exits the pump under a higher pressure and then passes to the sample injection valve. As the name suggests, the sample injection valve allows an operator to inject a sample into the LC system, where the sample will be carried along with the mobile phase.
After the sample injection valve, most LC systems include a column. A typical column usually consists of a piece of steel tubing which has been packed with a "packing" material. The "packing" consists of the particulate material inside the column. This material is usually made of silica- or polymer-based particles, which are often chemically bonded with a chemical function. When the sample is carried through the column (along with the mobile phase), the various components (solutes) in the sample migrate through the packing within the column at different rates (i.e., there is differential migration of the solutes). Because of the different rates of movement, the components gradually separate as they move through the column. A more detailed description of the separation process can be found, among other places, in Chapters 2 and 5 of Introduction to Modern Liquid Chromatography (2d ed. 1979) by L. R. Snyder and J. J. Kirkland, which chapters are incorporated by reference herein.
Once the sample (with its components now separated) leaves the column, it flows with the mobile phase past a detector. The detector detects the presence of specific molecules or compounds. As discussed in Chapter 4 of Introduction to Modern Liquid Chromatography, which chapter is incorporated by reference herein, two general types of detectors are used in LC applications. One type measures a change in some overall physical property of the mobile phase and the sample (such as their refractive index). The other type measures only some property of the sample (such as the absorption of ultraviolet radiation). In essence, a typical detector in an LC system can measure and provide an output in terms of mass per unit of volume (such as grams per milliliter) or mass per unit of time (such as grams per second) of the sample's components. From such an output signal, a "chromatograph" can be provided; the chromatograph can then be used by an operator to determine the chemical components present in the sample.
In FIG. 1, a block diagram illustrating the typical environment in which the present invention will be utilized is provided, with the basic and essential elements of a prior art LC system shown. A reservoir 1 contains a solvent or mobile phase 2. Tubing 3 connects the mobile phase 2 in the reservoir 1 to a pump 4. The pump 4 is connected via tubing to a sample injection valve 5 which, in turn, is connected via tubing to a first end of a column 6. The second end of the column 6 is then connected via tubing to a detector 7. After passing through the detector 7, the mobile phase 2 and the sample injected via injection valve 5 are transported via tubing into a second reservoir 8, which contains the chemical waste 9. As noted above, the sample injection valve 5 is used to inject a sample of a material to be studied into the LC system. In operation, the mobile phase 2 flows through the tubing 3, which is used to connect the various elements of the LC system together.
When the sample is injected via sample injection valve 5 in the LC system, the sample is carried by the mobile phase through the tubing into the column 6. As is well known in the art, the column 6 contains a packing material which acts to separate the constituent elements of the sample. After exiting the column 6, the sample (as separated via the column 6) then is carried to and enters a detector 7, which detects the presence or absence of various ions. The information obtained by the detector 7 can then be stored by well-known means (such as a personal computer programmed to do so) and used by an operator of the LC system to determine the constituent elements of the sample injected into the LC system.
In addition to the above components, many LC systems will include various filters, check valves, or the like in order to prevent contamination of the sample or damage to the LC system. It will be understood to those skilled in the art that, as used herein, the term "LC system" is intended in its broad sense to include all apparatus used in connection with liquid chromatography, whether made of only a few simple components or made of numerous, sophisticated components which are computer controlled or the like.
Because of the substantial amount of time and effort it often takes to set up and test a particular configuration of a LC system, a multiport selection valve is particularly useful. The use of appropriate multiport selection valves in an LC system allows the operator to design and configure a more comprehensive LC system which can use different mobile phases, different columns, and the like. Once plumbed, such a comprehensive LC system can be immediately used with a different column, for example, simply by using the appropriate multiport selection valve to switch the flow to the different column.
Most pumps used in the LC systems which are commercially available can generate relatively high pressures of up to around 10,000 to 15,000 psi. In many situations, an operator can obtain successful results by operating an LC system at low pressures of anywhere from just a few psi or so up to 1,000 psi or so. In other situations, however, an operator will find it desirable to operate an LC system at relatively "higher" pressures of over 1,000 psi. The operation and use of LC systems at such "higher" pressure levels is often referred to as "high pressure liquid chromatography" or "high performance liquid chromatography" (HPLC). In order to be suitable for HPLC applications, an LC component must be made to withstand the required pressures. Otherwise, the component may fail, thus potentially causing personal injury, the loss of valuable materials and research efforts, and the like. For these and other reasons, many components and fittings used in HPLC are made of stainless steel.
More recently, it has been realized that the use of stainless steel (and other metals) in the components of an LC system which come in contact with the mobile phase create potential drawbacks when dealing with biological samples. For example, the ions in a sample may attach themselves to the stainless steel material if the mobile phase comes in contact with the stainless steel. Similarly, ions from the metal components may detach and eventually flow past the detector, thus leading to potentially erroneous results. Hence, those portions of the LC components which come in contact with the mobile phase need to be biocompatible (i.e., chemically inert with respect to biological samples and the mobile phase carrying these samples) in many applications involving biological samples. Simply put, there is a need for biocompatible components of LC systems.
Generally speaking, multiport selection valves have been known for some time. The following is a brief summary of several earlier patents involving multiport selection valves. U.S. Pat. No. 3,961,534 describes a two-position rotary valve for injecting a sample into a LC system. This particular valve is switchable between a load position and an inject position. U.S. Pat. No. 4,158,630 describes an apparatus for delivering samples to a liquid chromatography system where the samples are loaded into sample loops via a loop selector valve. The loop selector valve includes a rotor which connects the inlet and outlet lines of the selected loop. In addition, a multiport valve which includes a stator and rotor assembly is used to selectively connect the various ports. This patent also mentions the use of an actuator motor to advance the valves automatically. U.S. Pat. Nos. 4,158,630 (Stearns) and 3,961,534 (Gundelfinger) are incorporated by reference herein as if fully set forth.
U.S. Pat. No. 4,444,066 describes a high pressure multiport valve for control of the injection of a sample into a liquid chromatography column. The valve operates in two positions and is said to require a minimum of movement between the two positions. In U.S. Pat. No. 4,655,095, a compound valve is described which can be used as a sample injector in a liquid chromatography system. The valve has a shaft including an axle bore on one end and a radial bore communicating with the axle bore. U.S. Pat. Nos. 4,444,066 (Ogle et al) and 4,655,095 (Russo et al) are incorporated by reference as if fully set forth herein.
In the past, multiport valves for high pressure LC applications were limited to valves made of metal or otherwise having metallic parts which contacted the mobile phase. Hence, such valves were not biocompatible. On the other hand, those multiport valves which were made of plastic materials (and were therefore biocompatible) could only be used at relatively low operating pressures; i.e., up to approximately 500 psi. Hence, there is a need for a multiport selection valve which is biocompatible and which can be used in relatively high pressure applications (such as those up to 2,000 psi or so) without leaking or otherwise failing.
An object of the present invention is to provide an efficient, effective and inexpensive multiport selection valve which is biocompatible.
Another object of the present invention is to provide the flexibility of establishing leak free fluid communication between a common port to any one of a plurality of selection ports.
It is another object of the present invention to provide a multiport selection valve that is biocompatible and can be used at relatively higher pressures of up to around 2,000 psi in a liquid chromatography system.
It is yet another object of the present invention to provide a multiport selection valve which maintains a low dead volume while connecting a common port to one of a plurality of selection ports.
It is yet another object of the present invention to allow a different selection port to be selected with a minimum of torque.
The above and other advantages of the present invention will become readily apparent to those skilled in the art from the following detailed description of the present invention, and from the attached drawings, which are briefly described below.